Tax of the human T-lymphotropic virus type I transactivates promoter of the MDR-1 gene.

The mdr-1 gene has been shown to confer resistance to chemotherapy of multiple drugs which share no obvious structural similarities. We and others have previously reported that some virus-associated malignant cells express high levels of MDR-1 (1,2), probably regulated by some viral proteins. In this study we have examined the role of Tax, the key protein of HTLV-1. An excellent correlation was found between the existence of HTLV-1 and the expression of MDR-1 among seven human T-cell lines. In the second part of the study, a 1. 76-kb DNA fragment representing the upstream regulatory elements of human mdr-1 gene was cloned into the CAT reporter plasmid. When the Tax expression plasmid was co-transfected with the MDR-1 reporter plasmid, a significant induction of CAT activity was observed. We conclude that Tax protein may up-regulate the expression of the mdr-1 gene.